3-Azabicyclo(3.1.0)hexane-2-carboxylic acid has been found to be an effective plant male gametocide: U.S. Pat. No. 4,047,930 (the compound is designated therein as 2-carboxy-3,4-methanopyrrolidine). The compound exists in the forms of two geometric (i.e., cis, trans) isomers. Each of these isomeric forms exists in the forms of optical isomers. The racemic mixtures of both of the geometric isomer forms are active as plant male gametocides. The naturally occurring, L, cis isomer is active as a plant male gametocide; the relative activities of each of the other optical isomer forms have not been determined. The L, cis isomer occurs naturally in the seeds of the American horse chestnut, Aesculus parviflora.
3-Azabicyclo(3.1.0)hexane-2-carboxylic acid now can be prepared synthetically by the following route:
(1) 1,2-cyclopropanedicarboxylic acid is treated with benzylamine to form 3-(benzyl)-3-azabicyclo(3.1.0)hexane-2,4-dione (I).
(2) I is selectively reduced to 3-(benzyl)-3-azabicyclo(3.1.0)hexane (II).
(3) II is catalytically hydrogenated to form 3-azabicyclo(3.1.0)hexane (III).
(4) III is chlorinated to give 3-chloro-3-azabicyclo(3.1.0)hexane (IV).
(5) A solution of IV is treated with a strong inorganic base and a lower alkanol, and solids are removed from the resulting reaction mixture, to give a solution of 3-azabicyclo(3.1.0)hex-2-ene (V).
(6) The solution of V is treated with an alkali metal bisulfite to form the 2-bisulfite adduct (VI) of 3-azabicyclo(3.1.0)hex-2-ene.
(7) The reaction mixture containing VI is treated with an alkali metal cyanide to form 3-azabicyclo(3.1.0)hexane-2-carbonitrile (VII).
(8) VII is treated with barium hydroxide to form the barium salt of 3-azabicyclo(3.1.0)hexane-2-carboxylic acid, which is treated with sulfuric acid to give a mixture of (.+-.-trans and .+-.-cis)-3-azabicyclo(3.1.0)hexane-2-carboxylic acid, from which the two racemic mixtures can be isolated, if desired.